Understanding tobacco flavor effects on waterpipe smokers' experiences and exposures Abstract: Waterpipe (WP) tobacco smoking (a.k.a. hookah, shisha, narghile) is increasing rapidly in the United States (US), particularly among young people. Time trends of WP smoking among youth in the US, show that WP smoking has become comparable to cigarette smoking among high- school students for the first time ever in 2014. Evidence suggests that WP smoking can lead to dependence, other tobacco use, and many of the known smoking-related diseases including cancer, cardiovascular disease and adverse pregnancy outcomes. These alarming trends led the Food and Drug Administration (FDA) in 2014 to propose including the WP under its regulatory authority, allowing the FDA to apply evidence-based regulatory approaches to control WP spread in the US. Given the salience of flavored tobacco in shaping the ?WP experience?, regulating WP tobacco flavor represents a promising approach for the FDA to curb WP use among US youth. This project aims to assist the FDA in these efforts by providing answers to specific questions pertinent to the potential of WP regulation through flavor. These include: - How would flavor manipulation affect the smoking experience and satisfaction of WP users at different stages of their smoking trajectory - How would smoking non-preferred flavor or unflavored WP tobacco reflects on smokers' exposure to nicotine, and dependence; and - How would flavor manipulation influence puffing behavior and exposure to toxicants such as carbon monoxide (CO) among WP smokers. Answers to these questions will help the FDA predict the impact of flavor regulation on WP experimentation and continued use. In this study, we will use clinical laboratory methods to answer these questions, where we will recruit two groups of WP smokers based on their use frequency: low (Beginners) vs. high frequency (Experienced) smokers (72/group; total 144; age 18-30). Each participant will undergo 3 WP smoking sessions that differ by flavor (preferred flavor; non-preferred flavor; unflavored), while measurement of WP satisfaction, dependence, harm perception, and exposure to nicotine and toxicants will be conducted. The response of WP smokers at different stages of their WP smoking trajectory (Beginners vs. Experienced) to flavor manipulation, will allow us to predict the effect of limiting flavors on a wide range of WP smokers. This project promises to provide the first evidence to guide the FDA in terms of the potential of regulating WP flavored tobacco on WP uptake and use in the US.